The Affiliated Hospital of Medical School, Ningbo University, Ningbo, China.
Department of Preventive Medicine, Zhejiang Provincial Key Laboratory of Pathological and Physiological Technology, School of Medicine, Ningbo University, Ningbo, China.
PLoS One. 2021 Apr 1;16(4):e0247423. doi: 10.1371/journal.pone.0247423. eCollection 2021.
Human parechoviruses (HPeVs) are human pathogens that usually cause diseases ranging from rash to neonatal sepsis in young children. HPeV1 and HPeV3 are the most frequently reported genotypes and their three-dimensional structures have been determined. However, there is a lack of systematic research on the antigenic epitopes of HPeVs, which are useful for understanding virus-receptor interactions, developing antiviral agents or molecular diagnostic tools, and monitoring antigenic evolution. Thus, we systematically predicted and compared the conformational epitopes of HPeV1 and HPeV3 using bioinformatics methods in the study. The results showed that both epitopes clustered into three sites (sites 1, 2 and 3). Site 1 was located on the "northern rim" near the fivefold vertex; site 2 was on the "puff"; and site 3 was divided into two parts, of which one was located on the "knob" and the other was close to the threefold vertex. The predicted epitopes highly overlapped with the reported antigenic epitopes, which indicated that the prediction results were accurate. Although the distribution positions of the epitopes of HPeV1 and HPeV3 were highly consistent, the residues varied largely and determined the genotypes. Three amino acid residues, VP3-91N, -92H and VP0-257S, were the key residues for monoclonal antibody (mAb) AM28 binding to HPeV1 and were also of great significance in distinguishing HPeV1 and HPeV3. We also found that two residues, VP1-85N and -87D, might affect the capability of mAb AT12-015 to bind to HPeV3.
人肠道病毒（HPeV）是人类病原体，通常会导致幼儿出现皮疹、新生儿败血症等疾病。HPeV1 和 HPeV3 是最常报道的基因型，其三维结构已被确定。然而，对于 HPeV 的抗原表位缺乏系统研究，这些表位对于了解病毒-受体相互作用、开发抗病毒药物或分子诊断工具以及监测抗原进化非常有用。因此，我们在研究中使用生物信息学方法系统地预测和比较了 HPeV1 和 HPeV3 的构象表位。结果表明，两个表位都聚集在三个部位（部位 1、2 和 3）。部位 1 位于五倍体顶点附近的“北缘”；部位 2 在“泡”上；部位 3 分为两部分，其中一部分位于“旋钮”上，另一部分靠近三倍体顶点。预测的表位与报道的抗原表位高度重叠，这表明预测结果是准确的。尽管 HPeV1 和 HPeV3 表位的分布位置高度一致，但残基差异很大，决定了基因型。三个氨基酸残基 VP3-91N、-92H 和 VP0-257S 是单克隆抗体（mAb）AM28 结合 HPeV1 的关键残基，对于区分 HPeV1 和 HPeV3 也具有重要意义。我们还发现两个残基 VP1-85N 和 -87D 可能影响 mAb AT12-015 结合 HPeV3 的能力。
